Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families

Synpolydactyly (SPD) is a limb malformation that shows a characteristic manifestation in both hands and feet. This condition is inherited as an autosomal dominant trait with reduced penetrance. We have recently mapped this locus centromeric to the HOXD8 intragenic marker and suggested the HOXD13 gene as a potential candidate for this condition. The genomic structure of HOXD13 established in this study consists of two exons that encodes a polypeptide of 335 amino acids. The downstream exon at the 3' end of this gene contains the homeodomain sequences that are highly conserved. Sixty-three bp upstream of this exon lies a stretch of intronic CA-repeats that proved to be polymorphic in two different populations. The upstream exon encodes 75% of the entire protein and contains a stretch of 15 normal alanines at its 5' end. Sequence comparison at this position in the homozygous affected individuals identified a total of 24 alanine residues that resulted from a duplication of nine polyalanines. In two unrelated SPD families, this duplication was directly transmitted from the affected parents to their affected, but not unaffected, offspring; in one family its size has remained constant for at least 150 years spanning over seven generations. The presence of this duplication confirmed the status of four normal gene carriers, one incomplete penetrance and two affected individuals who were recombinants for HOXD8 or HOXD13-CA repeat markers. This duplication was not present in 150 chromosomes of unrelated healthy subjects of two different populations.      

The influence of hands posture on mental rotation of hands and feet

Behavioural and functional neuroanatomy studies demonstrate that mental rotation of body parts is carried out through a sort of inner motor simulation. Here we examined whether changes of hands posture influence the mental rotation of hands and feet. Twenty healthy subjects were asked to verbally judge the laterality of hands and feet pictures in two different postural conditions. In one condition, subjects kept hands on their knees in anatomical position; in the other, their hands were kept in an unusual posture with intertwined fingers, behind the back. Results show that mental rotation of hands but not of feet was influenced by changes in hands posture. Indeed, while mental rotation of hands was faster in the front than in the back hands position, no similar effect was found when mentally rotating feet. Thus, sensory-motor and postural information coming from the body may influence mental rotation of body parts according to specific, somatotopic rules.     

Oto-palato-digital syndrome type II in two unrelated boys

We report on two boys with oto-palato-digital syndrome type II, characterized by growth retardation, bowed long bones, missing or hypoplastic fibulae, sclerosis of the skull base and wavy, irregular clavicles and ribs. The facial appearance is distinctive due to prominent forehead, widely spaced eyes, antimongologid slant of palpebral fissures, flattened nasal bridge and retrogenia. The mother of one patient showed a mild manifestation of oto-palato-digital syndrome type II. Only about 20 cases of this rare X-linked disorder have been reported so far. The similiarities and dissimilarities to oto-palato-digital syndrome type I are discussed.     

Differential influence of hands posture on mental rotation of hands and feet in left and right handers

The representation of the body in the brain is continuously updated with regard to peripheral factors such as position or movement of body parts. In the present study, we investigated the effects of arm posture on the mental rotation of hands and feet. Sixteen right-handed and ten left-handed participants verbally judged the laterality of visually presented pictures of hands and feet in two different postural conditions. In one condition they placed their right hand on their right knee and their left hand behind the back, in the other condition the hand position was reversed. For right-handed participants response times for the laterality judgment of right hands increased when participants kept their right hand behind the back. This was not found for images of the left hand nor for images of the feet. For the left-handed participants, there was no effect of arm posture on hand or feet stimulus judgments. Thus, the body-part posture effect on mental rotation was found to be specific for the side and the body part for which the posture was modified only in right-handed participants, but it was absent for left-handed participants. For both samples, we also found a progressive disruption of the mental rotation function depending on the view from which the body parts were seen (i.e. dorsal, thumb/big toe, palm/plantar, little finger/toe). Posture and view effects on body parts representations are discussed with respect to proprioception, handedness, visual familiarity and the influence of anatomical joint constraints on motor imagery.     

Marfan-like habitus and familial adenomatous polyposis in two unrelated males: a significant association?

Familial adenomatous polyposis (FAP) can be considered as a condition of the whole body as extracolonic features derived from all the three embryonic lineages are recorded with varying frequency in addition to the presence of multiple adenomas in the large intestine. Here, we describe two unrelated cases of FAP with unusual extracolonic phenotypes, namely several abnormalities of mesodermal origin strongly resembling Marfan syndrome (MFS) or a Marfan-like habitus. Conventional cytogenetic and FISH analysis did not reveal any gross chromosomal rearrangement on the long arm of chromosome 5 where the APC and FBN2 genes were located. However, in case 2 the FAP-causing mutation in the APC gene was found in the donor splice site of exon 4 and was shown to result in a frameshift and a premature termination codon. We propose that such connective tissue abnormalities may result from germline APC mutations in combination with specific genetic and/or environmental modifying factors.     

Adult-onset Still's disease with vesiculopustules on the hands and feet

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology characterized by an evanescent rash, intermittent spiking high fever, arthralgia, and a variety of systemic features. We describe a 46-yr-old woman with Still s disease who presented with a 2-month history of a symmetrical vesiculopustular eruptions only on both hands and feet. Skin biopsy specimens of both vesicle and pustule revealed fibrin thrombi deposition in the small dermal vessels with little inflammation, subepidermal bulla, and ischemic necrosis of the overlying epidermis, which were consistent with a vasculopathic reaction. Her skin lesions gradually disappeared in response to conventional AOSD therapy, as elevated serum ferritin levels, an index of disease activity, decreased. To the best of our knowledge, this is the first case of vesiculopustular lesions as a skin manifestation of AOSD.     

对称性双手多指、双足多趾畸形1例

先天性多指(趾)畸形又称重复指(趾),是在新生儿中常见的疾病.病因尚不明确,多指(趾)畸形在手与足的先天性畸形中较常见,有时可与并指、短指或其他先天性畸形同时存在,足部畸形趾以单个较多见,多生长在拇趾或小趾胖,而第2、3、4足趾处少见[1].有关对称性多指(趾)畸形并伴有家族遗传性的报道较少见.现将我科于2009年9月收治的1例有遗传倾向的先天性对称性多指及多趾畸形并伴有独立跖骨的病例报道如下.     

Osteosarcoma of the hands and feet: a distinct clinico-pathological subgroup

Osteosarcomas of hands or feet are rare, and seemingly these cases differ in presentation and behavior compared to those in usual locations. The clinico-pathological presentation of patients with osteosarcomas of the hand or foot was studied and compared with published cases. Forty osteosarcomas were identified among 4,221 cases, representing 0.95 % of all osteosarcomas. Thirty of these were well documented. Mean age at diagnosis was 43 years (hands) and 36 years (feet) and male–female ratio was 1.2:1 and 2.0:1, respectively. In the hand, 62 % of the osteosarcomas presented in the metacarpals and 23 % in the phalanges, and only two cases occurred in the carpal bones. Distribution in the foot was tarsal bones 56 %, metatarsal bones 33 %, and phalanges 11 %.Of the cases in the hand 54 % were of high grade and of those in the foot 71 %. Survival of osteosarcomas of the hand or foot was 81 %. Only patients with high-grade osteosarcoma died of the disease. Histological grade was the only significant variable related to survival. High-grade osteosarcoma of the hand or feet should be treated similar to those in conventional sites. Osteosarcomas of hands or feet are rare and in a relative high proportion are of low grade. Survival in high-grade cases is comparable to that in conventional sites.     

Mirror hands and feet: a further case of Laurin-Sandrow syndrome.

We report a girl with mirror hands and feet and associated groove of the nasal columella. She represents only the sixth reported case of this spectrum of congenital anomalies,first reported by Laurin and Sandrow.     

HOXD13 polyalanine tract expansion in classical synpolydactyly type Vordingborg

In 1927, Oluf Thomsen, in a classic paper, described a seven-generation family with autosomal dominant axial synpolydactyly (SPD)--the Vordingborgtyp of axis duplication and dysostosis. Expansion of a polyalanine tract in the HOXD13 gene is known to cause synpolydactyly. We have rediscovered part of the family described by Thomsen, and detected a 9 triplet polyalanine expansion within HOXD13segregating with the disorder. The phenotypic spectrum in mutation carriers ranged from severe to inapparent bone malformations. In the latter case, only dermatoglyphics revealed the genetic status.     

Radiographic appearance of sesamoid bones in the hands and feet of Malawian subjects.

Our aim was to determine the prevalence of sesamoid bones in adult black Malawians from radiographs of the hands and feet. A total of 255 radiographs from 85 men and 45 women aged 16-66 years were used: 126 of the hands and 129 of the feet. All the hand films revealed one sesamoid bone at the interphalangeal joint and two at the metacarpophalangeal joint of the thumb. All the foot films showed two sesamoid bones at the metatarsophalangeal joint of the big toe. Occasional sesamoid bones were found at the metacarpophalangeal and metatarsophalangeal joints of the index finger and the small toe, respectively. Only 4.8% of the hands had sesamoid bones at the metacarpophalangeal joint of the index finger, compared with reported percentages of between 35% and 64.2% in Caucasians. The present study also records, probably for the first time in Africans, an incidence of 10.8% of sesamoid bones occurring at the metatarsophalangeal joint of the small toe, which again is at variance with the reported range of 5.5-10% in Caucasians. This study provides anatomical data that will help in the diagnosis and management of disorders of sesamoid bones which are often overlooked in Africans.     

Distinct facial appearance with nasal hypoplasia, constipation, severe mental retardation and hypotonia in two unrelated young males

In this report we describe two unrelated young males with severe mental retardation, persisting hypotonia, and constipation. A maternal uncle of one of these two boys died at the age of 18 months and presented the same clinical symptoms. The triad mental retardation, hypotonia, constipation is a characteristic finding in the FG syndrome, an X-linked mental retardation syndrome. At the present time, there is increasing evidence that the FG syndrome-phenotype may be present in different XLMR conditions, e.g. the fragile X syndrome. In addition to the triad severe mental retardation, hypotonia, constipation, the present two male index patients had a characteristic facial appearance with nasal hypoplasia, relative microcephaly and pre-and postnatal overgrowth. The question is raised whether the present two males are examples of a specific entity within the FG-syndrome-like phenotype.     

Fetal activity following stimulation of the mother's abdomen,feet, and hands

Fetal activity during midgestation (M age=19.8 weeks) was studied in response to vibratory stimulation of the mother's abdomen (at the height of the fetal head), foot massage, hand massage, or control condition (no stimulation). Consistent with previous research conducted during midgestation, the fetuses of mothers who received two trials of 3-sec, 60-Hz vibratory stimulation did not show changes in movement. In contrast, the fetuses of mothers who received a 3-min foot massage showed greater movement than the control fetuses. However, stimulating the mother's hand (another highly innervated area) did not increase fetal activity. By late gestation (M age=35.4 weeks), vibratory stimulation resulted in increased fetal activity. These findings replicate previous research indicating that vibratory stimulation to the mother's abdomen does not elicit fetal activity until later in gestation. Furthermore, our findings indicate that stimulating the mothers' feet, but not the hands, can evoke fetal activity in midgestation.     

Symphalangism with multiple anomalies of the hands and feet: a new genetic trait

We report a new autosomal dominant condition involving hands and feet of an Arabic father and 5 of his 11 children. This trait is characterized by symphalangism, syndactyly, brachydactyly type D, clinodactyly, and hypoplasia of the thenar and hypothenar eminences. Affected persons had symphalangism and syndactyly plus some or all or part of the other anomalies. Symphalangism, the main defect in this syndrome, showed variable expressivity. A distinct dermatoglyphic pattern was observed in all affected relatives. Linkage studies were done; however, no linkage was demonstrated.